AU766705B2 - Multi-stage method for producing gas-filled microcapsules - Google Patents

Multi-stage method for producing gas-filled microcapsules Download PDF

Info

Publication number: AU766705B2
Authority: AU; Australia
Prior art keywords: process according; poly; oxyethylene; polymerization; gas
Prior art date: 1999-05-27
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.): Ceased

Application number

AU59627/00A

Other languages

English (en)

Other versions

AU5962700A (en

Inventor

Andreas Briel

Uwe Budde

Michael Gottfried

Jan-Peter Ingwersen

Kai Lovis

Hans-Ulrich Moritz

Georg Rossling

Wolfgang Schmidt

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Acusphere Inc

Original Assignee

Schering AG

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1999-05-27

Filing date

2000-05-23

Publication date

2003-10-23

2000-05-23 Application filed by Schering AG filed Critical Schering AG

2000-12-18 Publication of AU5962700A publication Critical patent/AU5962700A/en

2003-10-23 Application granted granted Critical

2003-10-23 Publication of AU766705B2 publication Critical patent/AU766705B2/en

2005-11-03 Assigned to ACUSPHERE, INC. reassignment ACUSPHERE, INC. Alteration of Name(s) in Register under S187 Assignors: SCHERING AKTIENGESELLSCHAFT

2020-05-23 Anticipated expiration legal-status Critical

Status Ceased legal-status Critical Current

Links

239000003094 microcapsule Substances 0.000 title claims abstract description 71
238000004519 manufacturing process Methods 0.000 title claims abstract description 41
238000000034 method Methods 0.000 claims abstract description 107
230000008569 process Effects 0.000 claims abstract description 84
238000006116 polymerization reaction Methods 0.000 claims abstract description 40
238000003756 stirring Methods 0.000 claims abstract description 32
239000000126 substance Substances 0.000 claims abstract description 10
-1 sulfate alkali salts Chemical class 0.000 claims description 49
229920000642 polymer Polymers 0.000 claims description 34
239000002245 particle Substances 0.000 claims description 29
239000006185 dispersion Substances 0.000 claims description 26
239000000178 monomer Substances 0.000 claims description 22
230000015572 biosynthetic process Effects 0.000 claims description 21
239000012429 reaction media Substances 0.000 claims description 16
239000000243 solution Substances 0.000 claims description 16
238000006243 chemical reaction Methods 0.000 claims description 15
235000014113 dietary fatty acids Nutrition 0.000 claims description 15
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239000004094 surface-active agent Substances 0.000 claims description 15
239000000463 material Substances 0.000 claims description 12
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 12
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 10
229920002451 polyvinyl alcohol Polymers 0.000 claims description 9
239000007864 aqueous solution Substances 0.000 claims description 8
125000006353 oxyethylene group Chemical group 0.000 claims description 7
235000019422 polyvinyl alcohol Nutrition 0.000 claims description 7
229920000036 polyvinylpyrrolidone Polymers 0.000 claims description 7
239000001267 polyvinylpyrrolidone Substances 0.000 claims description 7
235000013855 polyvinylpyrrolidone Nutrition 0.000 claims description 7
WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 6
230000002378 acidificating effect Effects 0.000 claims description 6
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229920002113 octoxynol Polymers 0.000 claims description 6
239000004372 Polyvinyl alcohol Substances 0.000 claims description 5
125000005907 alkyl ester group Chemical group 0.000 claims description 5
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 claims description 5
239000011541 reaction mixture Substances 0.000 claims description 5
JNYAEWCLZODPBN-JGWLITMVSA-N (2r,3r,4s)-2-[(1r)-1,2-dihydroxyethyl]oxolane-3,4-diol Chemical compound OC[C@@H](O)[C@H]1OC[C@H](O)[C@H]1O JNYAEWCLZODPBN-JGWLITMVSA-N 0.000 claims description 4
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SMZOUWXMTYCWNB-UHFFFAOYSA-N 2-(2-methoxy-5-methylphenyl)ethanamine Chemical compound COC1=CC=C(C)C=C1CCN SMZOUWXMTYCWNB-UHFFFAOYSA-N 0.000 claims description 2
NIXOWILDQLNWCW-UHFFFAOYSA-N 2-Propenoic acid Natural products OC(=O)C=C NIXOWILDQLNWCW-UHFFFAOYSA-N 0.000 claims description 2
JYFREZOLRUHBAQ-UHFFFAOYSA-N 2-cyano-4-methylpent-2-enoic acid Chemical compound CC(C)C=C(C#N)C(O)=O JYFREZOLRUHBAQ-UHFFFAOYSA-N 0.000 claims description 2
IJVRPNIWWODHHA-UHFFFAOYSA-N 2-cyanoprop-2-enoic acid Chemical compound OC(=O)C(=C)C#N IJVRPNIWWODHHA-UHFFFAOYSA-N 0.000 claims description 2
229920002307 Dextran Polymers 0.000 claims description 2
CERQOIWHTDAKMF-UHFFFAOYSA-N Methacrylic acid Chemical compound CC(=C)C(O)=O CERQOIWHTDAKMF-UHFFFAOYSA-N 0.000 claims description 2
229920003171 Poly (ethylene oxide) Polymers 0.000 claims description 2
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 claims description 2
229930006000 Sucrose Natural products 0.000 claims description 2
CZMRCDWAGMRECN-UGDNZRGBSA-N Sucrose Chemical compound O[C@H]1[C@H](O)[C@@H](CO)O[C@@]1(CO)O[C@@H]1[C@H](O)[C@@H](O)[C@H](O)[C@@H](CO)O1 CZMRCDWAGMRECN-UGDNZRGBSA-N 0.000 claims description 2
150000007513 acids Chemical class 0.000 claims description 2
150000001298 alcohols Chemical class 0.000 claims description 2
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
235000013681 dietary sucrose Nutrition 0.000 claims description 2
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 2
150000002191 fatty alcohols Chemical class 0.000 claims description 2
230000007062 hydrolysis Effects 0.000 claims description 2
238000006460 hydrolysis reaction Methods 0.000 claims description 2
229940072106 hydroxystearate Drugs 0.000 claims description 2
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229920000847 nonoxynol Polymers 0.000 claims description 2
SNQQPOLDUKLAAF-UHFFFAOYSA-N nonylphenol Chemical class CCCCCCCCCC1=CC=CC=C1O SNQQPOLDUKLAAF-UHFFFAOYSA-N 0.000 claims description 2
229920001983 poloxamer Polymers 0.000 claims description 2
235000002639 sodium chloride Nutrition 0.000 claims description 2
239000011780 sodium chloride Substances 0.000 claims description 2
229960004793 sucrose Drugs 0.000 claims description 2
OULAJFUGPPVRBK-UHFFFAOYSA-N tetratriacontan-1-ol Chemical class CCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCCO OULAJFUGPPVRBK-UHFFFAOYSA-N 0.000 claims description 2
GPRLSGONYQIRFK-MNYXATJNSA-N triton Chemical compound [3H+] GPRLSGONYQIRFK-MNYXATJNSA-N 0.000 claims description 2
150000002148 esters Chemical class 0.000 claims 3
229940068984 polyvinyl alcohol Drugs 0.000 claims 2
YNDGLMYLSGEDHX-UHFFFAOYSA-N 1,2,4,3-trioxathiane 3,3-dioxide Chemical compound O=S1(=O)OCCOO1 YNDGLMYLSGEDHX-UHFFFAOYSA-N 0.000 claims 1
102100026400 ADP/ATP translocase 4 Human genes 0.000 claims 1
101100108280 Homo sapiens SLC25A31 gene Proteins 0.000 claims 1
230000000996 additive effect Effects 0.000 claims 1
235000019441 ethanol Nutrition 0.000 claims 1
210000002966 serum Anatomy 0.000 claims 1
239000007789 gas Substances 0.000 description 52
238000002156 mixing Methods 0.000 description 13
239000002872 contrast media Substances 0.000 description 11
229940039231 contrast media Drugs 0.000 description 11
239000007788 liquid Substances 0.000 description 11
239000011859 microparticle Substances 0.000 description 9
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238000009826 distribution Methods 0.000 description 8
239000004815 dispersion polymer Substances 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000006260 foam Substances 0.000 description 6
239000003960 organic solvent Substances 0.000 description 6
JJJFUHOGVZWXNQ-UHFFFAOYSA-N enbucrilate Chemical compound CCCCOC(=O)C(=C)C#N JJJFUHOGVZWXNQ-UHFFFAOYSA-N 0.000 description 5
238000009432 framing Methods 0.000 description 5
239000011521 glass Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
239000002904 solvent Substances 0.000 description 5
239000008215 water for injection Substances 0.000 description 5
238000003745 diagnosis Methods 0.000 description 4
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239000000203 mixture Substances 0.000 description 4
238000000926 separation method Methods 0.000 description 4
238000002604 ultrasonography Methods 0.000 description 4
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
102000008100 Human Serum Albumin Human genes 0.000 description 3
108091006905 Human Serum Albumin Proteins 0.000 description 3
230000001133 acceleration Effects 0.000 description 3
230000008901 benefit Effects 0.000 description 3
238000002592 echocardiography Methods 0.000 description 3
210000004072 lung Anatomy 0.000 description 3
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238000003786 synthesis reaction Methods 0.000 description 3
238000012360 testing method Methods 0.000 description 3
YQEMORVAKMFKLG-UHFFFAOYSA-N 2-stearoylglycerol Chemical compound CCCCCCCCCCCCCCCCCC(=O)OC(CO)CO YQEMORVAKMFKLG-UHFFFAOYSA-N 0.000 description 2
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
239000002671 adjuvant Substances 0.000 description 2
238000004458 analytical method Methods 0.000 description 2
239000008280 blood Substances 0.000 description 2
210000004369 blood Anatomy 0.000 description 2
239000003814 drug Substances 0.000 description 2
238000001914 filtration Methods 0.000 description 2
238000009472 formulation Methods 0.000 description 2
230000006872 improvement Effects 0.000 description 2
230000036632 reaction speed Effects 0.000 description 2
239000000523 sample Substances 0.000 description 2
238000013341 scale-up Methods 0.000 description 2
238000007493 shaping process Methods 0.000 description 2
238000011146 sterile filtration Methods 0.000 description 2
239000003981 vehicle Substances 0.000 description 2
IMROMDMJAWUWLK-UHFFFAOYSA-N Ethenol Chemical compound OC=C IMROMDMJAWUWLK-UHFFFAOYSA-N 0.000 description 1
229920002858 MOWIOL ® 4-88 Polymers 0.000 description 1
238000001069 Raman spectroscopy Methods 0.000 description 1
229910000831 Steel Inorganic materials 0.000 description 1
239000003929 acidic solution Substances 0.000 description 1
230000009471 action Effects 0.000 description 1
230000002009 allergenic effect Effects 0.000 description 1
VBICKXHEKHSIBG-UHFFFAOYSA-N beta-monoglyceryl stearate Natural products CCCCCCCCCCCCCCCCCC(=O)OCC(O)CO VBICKXHEKHSIBG-UHFFFAOYSA-N 0.000 description 1
229920002988 biodegradable polymer Polymers 0.000 description 1
239000004621 biodegradable polymer Substances 0.000 description 1
230000005540 biological transmission Effects 0.000 description 1
230000036760 body temperature Effects 0.000 description 1
238000007707 calorimetry Methods 0.000 description 1
230000000747 cardiac effect Effects 0.000 description 1
230000002612 cardiopulmonary effect Effects 0.000 description 1
239000003795 chemical substances by application Substances 0.000 description 1
238000001246 colloidal dispersion Methods 0.000 description 1
238000001816 cooling Methods 0.000 description 1
239000011258 core-shell material Substances 0.000 description 1
238000007872 degassing Methods 0.000 description 1
230000001419 dependent effect Effects 0.000 description 1
239000000032 diagnostic agent Substances 0.000 description 1
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238000000502 dialysis Methods 0.000 description 1
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239000002270 dispersing agent Substances 0.000 description 1
238000005538 encapsulation Methods 0.000 description 1
238000005187 foaming Methods 0.000 description 1
238000004108 freeze drying Methods 0.000 description 1
239000000499 gel Substances 0.000 description 1
SVUQHVRAGMNPLW-UHFFFAOYSA-N glycerol monostearate Natural products CCCCCCCCCCCCCCCCC(=O)OCC(O)CO SVUQHVRAGMNPLW-UHFFFAOYSA-N 0.000 description 1
230000005484 gravity Effects 0.000 description 1
210000003709 heart valve Anatomy 0.000 description 1
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238000012552 review Methods 0.000 description 1
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Classifications

- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/06—Making microcapsules or microballoons by phase separation
- B01J13/14—Polymerisation; cross-linking
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K49/00—Preparations for testing in vivo
- A61K49/22—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations
- A61K49/222—Echographic preparations; Ultrasound imaging preparations ; Optoacoustic imaging preparations characterised by a special physical form, e.g. emulsions, liposomes
- A61K49/223—Microbubbles, hollow microspheres, free gas bubbles, gas microspheres
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J13/00—Colloid chemistry, e.g. the production of colloidal materials or their solutions, not otherwise provided for; Making microcapsules or microballoons
- B01J13/02—Making microcapsules or microballoons
- B01J13/04—Making microcapsules or microballoons by physical processes, e.g. drying, spraying
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
- Y10T428/2985—Solid-walled microcapsule from synthetic polymer
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T428/00—Stock material or miscellaneous articles
- Y10T428/29—Coated or structually defined flake, particle, cell, strand, strand portion, rod, filament, macroscopic fiber or mass thereof
- Y10T428/2982—Particulate matter [e.g., sphere, flake, etc.]
- Y10T428/2984—Microcapsule with fluid core [includes liposome]
- Y10T428/2985—Solid-walled microcapsule from synthetic polymer
- Y10T428/2987—Addition polymer from unsaturated monomers only

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Dispersion Chemistry (AREA)
Animal Behavior & Ethology (AREA)
Veterinary Medicine (AREA)
Public Health (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Health & Medical Sciences (AREA)
Life Sciences & Earth Sciences (AREA)
Epidemiology (AREA)
Physics & Mathematics (AREA)
Radiology & Medical Imaging (AREA)
Acoustics & Sound (AREA)
Engineering & Computer Science (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Pharmacology & Pharmacy (AREA)
Bioinformatics & Cheminformatics (AREA)
Manufacturing Of Micro-Capsules (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
Polymerisation Methods In General (AREA)
Medicinal Preparation (AREA)

AU59627/00A 1999-05-27 2000-05-23 Multi-stage method for producing gas-filled microcapsules Ceased AU766705B2 (en)

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date	Title
DE19925311A DE19925311B4 (de)	1999-05-27	1999-05-27	Mehrstufen-Verfahren zur Herstellung von gasgefüllten Mikrokapseln
DE19925311		1999-05-27
PCT/DE2000/001678 WO2000072888A1 (de)	1999-05-27	2000-05-23	Mehrstufen-verfahren zur herstellung von gasgefüllten mikrokapseln

Publications (2)

Publication Number	Publication Date
AU5962700A AU5962700A (en)	2000-12-18
AU766705B2 true AU766705B2 (en)	2003-10-23

Family

ID=7910041

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
AU59627/00A Ceased AU766705B2 (en)	1999-05-27	2000-05-23	Multi-stage method for producing gas-filled microcapsules

Country Status (29)

Country	Link
US (1)	US6652782B1 (no)
EP (1)	EP1180043B1 (no)
JP (1)	JP2003500458A (no)
KR (1)	KR100681369B1 (no)
CN (1)	CN1189218C (no)
AT (1)	ATE245034T1 (no)
AU (1)	AU766705B2 (no)
BG (1)	BG106137A (no)
BR (1)	BR0011543A (no)
CA (1)	CA2373869A1 (no)
CZ (1)	CZ297351B6 (no)
DE (2)	DE19925311B4 (no)
DK (1)	DK1180043T3 (no)
EA (1)	EA004220B1 (no)
EE (1)	EE200100630A (no)
ES (1)	ES2203496T3 (no)
HK (1)	HK1050492A1 (no)
HR (1)	HRP20010942A2 (no)
HU (1)	HUP0201640A2 (no)
IL (1)	IL146466A0 (no)
MX (1)	MXPA01011998A (no)
NO (1)	NO322312B1 (no)
NZ (1)	NZ515147A (no)
PL (1)	PL195106B1 (no)
PT (1)	PT1180043E (no)
SK (1)	SK16912001A3 (no)
WO (1)	WO2000072888A1 (no)
YU (1)	YU84101A (no)
ZA (1)	ZA200110482B (no)

Families Citing this family (6)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE19952738A1 (de) *	1999-10-27	2001-05-23	Schering Ag	Verbesserte Suspensionen von Ultraschallkontrastmitteln
DE10065068A1 (de) *	2000-12-21	2002-07-04	Schering Ag	Mehrstufen-Verfahren zur Herstellung von gasgefüllten Mikrokapseln mit definiert enger Größenverteilung durch definierte Fremdbegasung während des Mikrokapselaufbaus
SE0302794D0 (sv) *	2003-10-24	2003-10-24	Per Hansson	Novel microparticles for ultrasound contrast imaging and drug delivery
DE602005021057D1 (de)	2004-01-20	2010-06-17	Toronto E	Hochfrequenz-ultraschall-darstellung mit kontrastmitteln
CN1984708B (zh) *	2004-06-29	2014-01-29	皇家飞利浦电子股份有限公司	微球体
ITMI20110784A1 (it) *	2011-05-09	2012-11-10	Sipcam Spa	Processo per l'ottenimento di microcapsule

Family Cites Families (11)

* Cited by examiner, † Cited by third party
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DE4219724A1 (de) *	1992-06-13	1993-12-16	Schering Ag	Verwendung von Mikrokapseln als Kontrastmittel für die Farbdoppler-Sonographie
HU221485B (en) *	1988-02-05	2002-10-28	Schering Ag	Ultrasound contrast media consisting of microparticles and process for producing the same
DE4004430A1 (de)	1990-02-09	1991-08-14	Schering Ag	Aus polyaldehyden aufgebaute kontrastmittel
DE4219723A1 (de)	1992-06-13	1993-12-16	Schering Ag	Mikropartikel, Verfahren zu deren Herstellung, sowie die Verwendung dieser in der Diagnostik
DE4232755A1 (de)	1992-09-26	1994-03-31	Schering Ag	Mikropartikelpräparationen aus biologisch abbaubaren Mischpolymeren
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1999
- 1999-05-27 DE DE19925311A patent/DE19925311B4/de not_active Expired - Fee Related
2000
- 2000-05-23 IL IL14646600A patent/IL146466A0/xx unknown
- 2000-05-23 WO PCT/DE2000/001678 patent/WO2000072888A1/de active IP Right Grant
- 2000-05-23 US US09/979,554 patent/US6652782B1/en not_active Expired - Fee Related
- 2000-05-23 DE DE50002914T patent/DE50002914D1/de not_active Expired - Fee Related
- 2000-05-23 MX MXPA01011998A patent/MXPA01011998A/es active IP Right Grant
- 2000-05-23 ES ES00945561T patent/ES2203496T3/es not_active Expired - Lifetime
- 2000-05-23 JP JP2000620994A patent/JP2003500458A/ja active Pending
- 2000-05-23 AT AT00945561T patent/ATE245034T1/de not_active IP Right Cessation
- 2000-05-23 HU HU0201640A patent/HUP0201640A2/hu unknown
- 2000-05-23 CA CA002373869A patent/CA2373869A1/en not_active Abandoned
- 2000-05-23 BR BR0011543-6A patent/BR0011543A/pt not_active IP Right Cessation
- 2000-05-23 EA EA200101154A patent/EA004220B1/ru not_active IP Right Cessation
- 2000-05-23 EP EP00945561A patent/EP1180043B1/de not_active Expired - Lifetime
- 2000-05-23 SK SK1691-2001A patent/SK16912001A3/sk unknown
- 2000-05-23 KR KR1020017015097A patent/KR100681369B1/ko not_active IP Right Cessation
- 2000-05-23 EE EEP200100630A patent/EE200100630A/xx unknown
- 2000-05-23 AU AU59627/00A patent/AU766705B2/en not_active Ceased
- 2000-05-23 YU YU84101A patent/YU84101A/sh unknown
- 2000-05-23 CZ CZ20014235A patent/CZ297351B6/cs not_active IP Right Cessation
- 2000-05-23 NZ NZ515147A patent/NZ515147A/en unknown
- 2000-05-23 PT PT00945561T patent/PT1180043E/pt unknown
- 2000-05-23 CN CNB008110212A patent/CN1189218C/zh not_active Expired - Fee Related
- 2000-05-23 DK DK00945561T patent/DK1180043T3/da active
- 2000-05-23 PL PL00351873A patent/PL195106B1/pl not_active IP Right Cessation
2001
- 2001-11-23 BG BG106137A patent/BG106137A/bg unknown
- 2001-11-26 NO NO20015745A patent/NO322312B1/no unknown
- 2001-12-20 ZA ZA200110482A patent/ZA200110482B/en unknown
- 2001-12-21 HR HR20010942A patent/HRP20010942A2/hr not_active Application Discontinuation
2003
- 2003-04-15 HK HK03102710A patent/HK1050492A1/xx not_active IP Right Cessation

Also Published As

Publication number	Publication date
EE200100630A (et)	2003-02-17
HUP0201640A2 (en)	2002-08-28
AU5962700A (en)	2000-12-18
NZ515147A (en)	2003-07-25
DE50002914D1 (de)	2003-08-21
CZ297351B6 (cs)	2006-11-15
DE19925311A1 (de)	2000-11-30
CA2373869A1 (en)	2000-12-07
NO322312B1 (no)	2006-09-11
EP1180043A1 (de)	2002-02-20
EP1180043B1 (de)	2003-07-16
CN1377284A (zh)	2002-10-30
ES2203496T3 (es)	2004-04-16
YU84101A (sh)	2004-07-15
CN1189218C (zh)	2005-02-16
BG106137A (bg)	2002-07-31
DE19925311B4 (de)	2004-06-09
EA004220B1 (ru)	2004-02-26
PL195106B1 (pl)	2007-08-31
HK1050492A1 (en)	2003-06-27
NO20015745L (no)	2002-01-08
MXPA01011998A (es)	2002-06-04
CZ20014235A3 (cs)	2002-04-17
NO20015745D0 (no)	2001-11-26
KR100681369B1 (ko)	2007-02-12
EA200101154A1 (ru)	2002-06-27
PT1180043E (pt)	2003-11-28
PL351873A1 (en)	2003-06-30
ATE245034T1 (de)	2003-08-15
KR20020013894A (ko)	2002-02-21
DK1180043T3 (da)	2003-11-10
IL146466A0 (en)	2002-07-25
BR0011543A (pt)	2002-03-05
US6652782B1 (en)	2003-11-25
JP2003500458A (ja)	2003-01-07
ZA200110482B (en)	2003-04-24
HRP20010942A2 (en)	2003-12-31
WO2000072888A1 (de)	2000-12-07
SK16912001A3 (sk)	2002-04-04

Legal Events

Date	Code	Title	Description
2001-04-26	MK6	Application lapsed section 142(2)(f)/reg. 8.3(3) - pct applic. not entering national phase
2002-01-17	TH	Corrigenda	Free format text: IN VOL 15, NO 12, PAGE(S) 2367-2373 UNDER THE HEADING APPLICATIONS LAPSED, REFUSED OR WITHDRAWN PLEASE DELETE ALL REFERENCE TO APPLICATION NO. 59627/00
2004-02-19	FGA	Letters patent sealed or granted (standard patent)

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EP0885615B1 (en)	2003-03-26	Protein encapsulated insoluble gas microsperes and their preparation and use as ultrasonic imaging agents
JPH0720545B2 (ja)	1995-03-08	蛋白質で封入された微小気泡を調整するための連続超音波処理方法
US20030157023A1 (en)	2003-08-21	Microcapsules comprising functionalised polyalkylcyanoacrylates
AU766705B2 (en)	2003-10-23	Multi-stage method for producing gas-filled microcapsules
US20020172762A1 (en)	2002-11-21	Multi-stage process for the production of gas-filled microcapsules with defined narrow size distribution by defined external gassing during the build-up of microcapsules